Background Ultrasound is essential for accurate pregnancy dating, but its implementation in low- and middle-income countries is hindered by cost, infrastructure, and training barriers. The implementation of point-of-care ultrasound (POCUS) with artificial intelligence (AI) technology to accurately estimate gestational age can potentially address these barriers. We describe a protocol to evaluate the acceptability, feasibility, and fidelity of integrating AI-enabled POCUS for gestational age dating into routine antenatal care (ANC) in Zambia’s Lusaka Province. Methods PIKABU (Piloting Integration, Knowledge and Acceptability of Baby Ultrasounds) is a multi-year pilot program to introduce and maintain AI-enabled POCUS in six ANC facilities across three districts. To evaluate these activities, we designed a prospective, mixed methods evaluation to assess acceptability, feasibility, and fidelity. Informed by the Consolidated Framework for Implementation Research, the evaluation comprises six separate components: focus-group discussions, in-depth interviews, patient register reviews, time motion studies, implementation strategy assessments, and patient exit surveys. Participants include patients, community members, and healthcare providers. By collecting baseline and follow-up data every four months, we are able to measure these outcomes in longitudinal fashion. Discussion Integrating portable, AI-enabled POCUS into routine ANC can improve gestational age dating and improve maternal health services in resource limited settings. Through its assessment of the acceptability, feasibility, and fidelity, this study provides novel insights about service implementation. Our findings are expected to inform policy and programs considering AI-enabled POCUS and support broader adoption across a range of healthcare settings.

INTRODUCTION:We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS:Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS:Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS:Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Globally, more than two million perinatal deaths occur annually attributable to the intrapartum period, the vast majority occurring in low- and middle-income countries (LMICs). We sought to ascertain the incidence of adverse neonatal intrapartum-related outcomes and associated risk factors in tertiary referral centers in LMICs. The Limiting Adverse Birth Outcomes in Resource-limited settings (LABOR) Study was a prospective intrapartum observational cohort of women and their fetuses in Ghana, India and Zambia enrolled from 2019 to 2022 and followed through 42 days postpartum. Women with a singleton pregnancy admitted to the labor ward for a vaginal birth were eligible for inclusion; additionally, women admitted for a cesarean birth were eligible if they also had signs/symptoms of labor, elevated blood pressure or fever on admission. Among the 16,369 eligible participants, all 16,369 were approached; of these, 2315 refused and 1982 were excluded. Of the 12,072 enrolled, we excluded an additional 1736 with pre-labor Cesarean birth, analyzing a cohort of 10,336 women for this manuscript. Our primary outcome was a composite of these secondary outcomes: intrapartum stillbirth, neonatal death, intrapartum-related neonatal encephalopathy and culture-proven early onset neonatal sepsis. We estimated the incidence of outcomes using binomial proportions and the adjusted risk of outcomes associated with baseline factors using generalized linear models. We included 10,336 women with a median age of 27; 1788 (17·3

Women living with HIV face an increased burden of spontaneous preterm birth (sPTB); however, the underlying immunological mechanisms of sPTB and its association with HIV infection are poorly understood. Although the limited earlier literature implicates sphingosine-1-phosphate (S1P), a lysosphingolipid signaling molecule, in reproductive biology, the association of S1P signaling with HIV and sPTB has not been investigated. We examined whether two S1P signaling components, S1P receptors and sphingosine kinases, are expressed in the female reproductive tract and whether levels are associated with HIV status or spontaneous preterm birth. We quantified the mRNA expression of sphingosine-1-phosphate receptors 1 and 3 (S1PR1/S1PR3) and sphingosine kinases 1 and 2 (SPHK1/SPHK2) in 167 banked vaginal swab specimens collected between 14 and 26 weeks of gestation in a longitudinal pregnancy cohort in Lusaka, Zambia. We evaluated the expression of S1PR1, S1PR3, SPHK1, and SPHK2 by real-time quantitative reverse transcription PCR (RT-qPCR) in four groups (n = 41–42 each): women without HIV (WWoH) with term birth (≥37 weeks of gestation; TB), WWoH with spontaneous preterm birth (<37 weeks of gestation, sPTB), women with HIV (WWH) with TB, and WWH with sPTB. We found that S1P receptors and sphingosine kinases are expressed in the female reproductive tract. SPHK1 and SPHK2 mRNA expression were generally comparable among women independent of HIV status or birth outcome, though SPHK2 trended toward higher expression in women with HIV and women with sPTB. In contrast, S1PR1 mRNA trended toward higher expression in WWH vs. WWoH overall, as well as in WWH vs. WWoH among women with sPTB. Similarly, S1PR3 mRNA expression was greater in women with HIV than in women without HIV, and WWH, both with TB and sPTB, had higher S1PR3 mRNA expression than WWoH with TB. Perturbations in S1PR1 and S1PR3 mRNA expression may be associated with inflammation related to HIV infection and spontaneous preterm birth, suggesting that further studies of S1P signaling in pregnancy, especially among women with HIV, are warranted.

BACKGROUND:Third-trimester fetal ultrasound demonstrating abdominal circumference (AC) and estimated fetal weight (EFW) ≥90th percentile is associated with delivery of a large-for-gestational age (LGA) newborn; however, the clinical significance of discordance between these measures is unclear. OBJECTIVE:To evaluate the association between discordant AC and EFW percentiles and adverse perinatal outcomes. STUDY DESIGN:We conducted a retrospective cohort study of singleton pregnancies with a growth ultrasound performed between 32w0d and 36w6d at a single academic center (2017-2024). Fetuses were categorized into four groups based on 90th percentile thresholds for EFW and AC: (1) both <90th percentile (reference), (2) isolated large EFW (≥90th, AC<90%), (3) isolated large AC (≥90th, EFW<90%), and (4) both ≥90th percentile. The primary outcome was LGA birth (birthweight ≥90% by Fenton curve). Secondary outcomes included macrosomia (birthweight ≥4000 g), primary cesarean delivery, and shoulder dystocia. Using marginal standardization (parametric G-formula), we estimated adjusted risks, relative risks (aRR), and risk differences controlling for maternal age, body mass index, parity, and diabetes status. RESULTS:Among 13,592 eligible pregnancies, 75.7% had both EFW and AC<90th, 9.7% had isolated large EFW or AC, and 14.6% had both ≥90th percentile. Overall, 12.6% of neonates were LGA. Compared with the reference group, adjusted risk of LGA rose to 17.9% for isolated large AC (aRR 4.3, 95% confidence interval [CI] 3.6-5.1), 21.5% for isolated large EFW (aRR 5.2, 95% CI 4.1-6.5), and 48.2% when both AC and EFW were ≥90th percentile (aRR 11.4, 95% CI 10.2-12.8). Similar stepwise trends were observed for macrosomia, primary cesarean delivery, and shoulder dystocia. Associations were consistent across sensitivity analyses, including stratification by diabetes status. CONCLUSION:Compared to both AC and EFW <90th percentile, isolated third-trimester AC or EFW ≥90th percentile is associated with adverse perinatal outcomes. Patients with an isolated large AC should be counseled regarding these elevated perinatal risks.

OBJECTIVE:To evaluate the association between maternal HIV infection and preeclampsia. We hypothesized that maternal HIV infection would be associated with a lower risk of preeclampsia, potentially due to HIV-related immunomodulatory effects. METHODS:We combined participants from one observational cohort and two randomized trials conducted at the same facilities in Lusaka, Zambia between 2015 and 2022. The exposure of interest was maternal HIV infection, and the primary outcome was preeclampsia, defined as 1) new-onset (at or after 20 weeks of gestation) hypertension (systolic blood pressure [BP] 140 mm Hg or higher or diastolic BP 90 mm Hg or higher) with concurrent proteinuria (1+ or higher), 2) new onset proteinuria (1+ or higher) in participants with chronic hypertension in the absence of urinary tract infection, or 3) diagnosis of severe preeclampsia. We defined severe preeclampsia as 1) new-onset severe-range BP (systolic 160 mm Hg or higher or diastolic 110 mm Hg or higher), 2) eclamptic seizure, or 3) clinician-initiated preterm delivery (before 37 weeks of gestation) for preeclampsia. Using marginal standardization (parametric g-formula), we estimated the risk of preeclampsia associated with HIV infection. Antiretroviral therapy (ART) exposure and HIV disease severity (viral load, CD4 counts) were assessed as effect modifiers. RESULTS:Of 4,078 women included in the combined cohort, 186 (4.6%) were diagnosed with preeclampsia, including 43 (2.7%) of 1,590 women with HIV infection and 143 (5.8%) of 2,488 women without HIV infection. Of those with HIV infection, 73.2% were on prepregnancy ART, and 56.7% had an undetectable viral load at study enrollment (median 15 weeks). In analyses standardizing for maternal age, nulliparity, and calendar time of enrollment, HIV infection was associated with lower preeclampsia risk (relative risk 0.42; 95% CI, 0.26-0.59; risk difference -3.5%; 95% CI, -4.9 to -2.1). This reduced risk persisted when stratifying by prepregnancy ART exposure, detectable viral load, and CD4 count at enrollment; findings were similar when applying the more stringent definition of severe preeclampsia. CONCLUSION:In this well-phenotyped cohort, women with HIV infection were less likely to have preeclampsia compared with those without HIV infection.

BACKGROUND: The Multi-Omics for Mothers and Infants consortium aims to improve birth outcomes. Preterm birth is a major obstetrical complication globally and causes significant infant and childhood morbidity and mortality. OBJECTIVE: We analyzed placental samples (basal plate, placenta or chorionic villi, and the chorionic plate) collected by the 5 Multi-Omics for Mothers and Infants sites, namely The Alliance for Maternal and Newborn Health Improvement Bangladesh, The Alliance for Maternal and Newborn Health Improvement Pakistan, The Alliance for Maternal and Newborn Health Improvement Tanzania, The Global Alliance to Prevent Prematurity and Stillbirth Bangladesh, and The Global Alliance to Prevent Prematurity and Stillbirth Zambia. The goal was to analyze the morphology and gene expression of samples collected from preterm and uncomplicated term births. STUDY DESIGN: The teams provided biopsies from 166 singleton preterm (<37 weeks' gestation) and 175 term (>= 37 weeks' gestation) deliveries. The samples were fixed in formalin and paraffin embedded. Tissue sections from these samples were stained with hematoxylin and eosin and subjected to morphologic analyses. Other placental biopsies (n=35 preterm, 21 term) were flash frozen, which enabled RNA purification for bulk transcriptomics. RESULTS: The morphologic analyses revealed a surprisingly high rate of inflammation that involved the basal plate, placenta or chorionic villi, and the chorionic plate. The rate of inflammation in chorionic villus samples, likely attributable to chronic villitis, ranged from 25% (Pakistan site) to 60% (Zambia site) of cases. Leukocyte infiltration in this location vs in the basal plate or chorionic plate correlated with preterm birth. Our transcriptomic analyses identified 267 genes that were differentially expressed between placentas from preterm vs those from term births (123 upregulated, 144 downregulated). Mapping the differentially expressed genes onto single-cell RNA sequencing data from human placentas suggested that all the component cell types, either singly or in subsets, contributed to the observed dysregulation. Consistent with the histopathologic findings, gene ontology analyses highlighted the presence of leukocyte infiltration or activation and inflammatory responses in both the fetal and maternal compartments. CONCLUSION: The relationship between placental inflammation and preterm birth is appreciated in developed countries. In this study, we showed that this link also exists in developing geographies. In addition, among the participating sites, we found geographic- and population- based differences in placental inflammation and preterm birth, suggesting the importance of local factors.

Introduction Studies of gestational weight gain (GWG) and adverse pregnancy outcomes seldom focus on low-to-middle-income countries (LMICs), despite their high burden of morbidity and mortality. We examined GWG patterns and adverse pregnancy outcomes in a consortium of pregnancy cohorts from LMICs.Methods We analysed data from five observational pregnancy cohorts in Bangladesh (two cohorts), India, Pakistan and Zambia. The study population comprised 15 286 singleton pregnancies with two or more maternal antenatal weight measurements. We estimated reference values for GWG using longitudinal models and calculated weight gain for gestational age Z-scores. We then estimated the associated risks of preterm birth, low birth weight, and small for gestational age, stratified by maternal body mass index (BMI), using marginal generalised linear models and plotted non-linear trends in the associations.Results The median baseline maternal and gestational age were 24 years (IQR, 21–28) and 13 weeks (IQR 11–16), respectively, with 23% of participants having underweight BMI. The median GWG was 6.8 kg (4.2–9.4) and varied across cohorts from 6.1 kg (3.7–8.5; Bangladesh) to 7.0 kg (4.0–10.0; Zambia). The risk of preterm birth (13%) increased with lower GWG Z-scores among underweight (adjusted risk ratio (ARR), 1.4; 95% CI, 1.1 to 1.9 for lowest Z-score group) and normal BMI participants (ARR, 1.1; 95% CI, 1.0 to 1.2). The risk of low birth weight (25%) increased with lower GWG Z-scores in all BMI strata except obese participants (ARR, 1.7; 95% CI 1.5 to 1.9 among underweight). The risk of small for gestational age (36%) increased with lower GWG Z-scores in all BMI strata (ARR, 1.3; 95% CI 1.2 to 1.4 among underweight). In secondary analyses, alternative measures of GWG (adequacy ratio; INTERGROWTH-21st) had associations that were consistent with those from our study-specific Z-scores, except for a less clear association between preterm birth and INTERGROWTH-21st Z-score.Conclusion GWG was associated with preterm birth, low birth weight and small for gestational age. Early pregnancy BMI modified the association between GWG and outcomes in the study setting.

(Abstracted from JAMA 2024;332:649–657) Gestational age (GA) is critical for guiding obstetric decisions related to antenatal care and delivery. In high-income countries, GA is typically measured via fetal biometry using high-resolution ultrasound machines operated by credentialed sonographers.

Doubly robust estimators have gained popularity in the field of causal inference due to their ability to provide consistent point estimates when either an outcome or an exposure model is correctly specified. However, for nonrandomized exposures, the influence function based variance estimator frequently used with doubly robust estimators of the average causal effect is only consistent when both working models (ie, outcome and exposure models) are correctly specified. Here, the empirical sandwich variance estimator and the nonparametric bootstrap are demonstrated to be doubly robust variance estimators. That is, they are expected to provide valid estimates of the variance leading to nominal confidence interval coverage when only 1 working model is correctly specified. Simulation studies illustrate the properties of the influence function based, empirical sandwich, and nonparametric bootstrap variance estimators in the setting where parametric working models are assumed. Estimators are applied to data from the Improving Pregnancy Outcomes with Progesterone (IPOP) study to estimate the effect of maternal anemia on birth weight among women with HIV.

Objectives: Maternal HIV is associated with preterm birth (PTB). In resource-rich settings, spontaneous preterm birth (SPTB) has been linked to biomarkers of stress. We examined the association between allostatic load and SPTB among women with HIV. Methods: In a nested case-cohort analysis of a randomized trial of intramuscular progesterone to prevent PTB in women with HIV in Lusaka, Zambia, we measured 15 midtrimester plasma biomarkers from 4 domains: cardiovascular, immune, metabolic, and neuroendocrine. SPTB was defined as delivery <37wks preceded by spontaneous labor or membrane rupture. A composite ALI was calculated by summing Z-scores from all markers (ALI-15); another was calculated from a 7 marker subset (ALI-7) with Z-score differences >0.1 between outcome groups. We estimated SPTB time-to-event curves and hazard ratios (HR) between ALI quartiles. Results: Of 800 women enrolled in IPOP (2015-2017), 51 (6%) had SPTB. We randomly selected 107 participants, including 6 with SPTB (cases). We then selected all remaining cases (n=45), yielding a final sample of 152. Z-score distributions of systolic blood pressure, heart rate, HDL, triglycerides, hemoglobin A1C, albumin, and 25-OH Vitamin D were included in ALI-7. Participants in the fourth quartile of ALI-7 were more likely to experience SPTB (HR 2.49, 95% CI 1.15-5.40) than participants in the second quartile; this association was attenuated when quartile groups were defined by ALI-15 (HR 1.24, 95% CI 0.59-2.60). Conclusions: High ALI among women with HIV was associated with SPTB. A seven marker ALI appeared a more meaningful indicator of risk than one composed of all measured markers.

Adverse pregnancy outcomes (APOs) such as prematurity, low birth weight, stillbirth, and birth defects remain significant global health challenges. While many risk factors are known, APOs encompass a wide range of outcomes with diverse, sometimes poorly understood etiologies. Pregnancy-related acute kidney injury (PR-AKI) and liver injury are particularly associated with increased maternal and fetal mortality. This study investigated the association between hematological parameters, kidney and liver injury markers and adverse pregnancy outcomes. This cross-sectional study involved 714 pregnant women aged 18–40 years, conducted between August 2021 and August 2022. Maternal blood samples were collected before and after delivery to compare hematological parameters. Kidney and liver injury markers were measured using standard methods. The study analysed the association of these parameters with adverse pregnancy outcomes. The median age of participants was 24 years (Q1, Q3: 21, 26). Women with adverse pregnancy outcomes had statistically significant serum creatinine levels [0.52 mg/dL (0.45, 0.58)] compared to those without [0.50 mg/dL (0.44, 0.56)], although the difference was not clinically significant. Elevated Aspartate Transaminase (AST) levels (>90th percentile) were statistically associated with adverse pregnancy outcomes. Pairwise comparisons with Bonferroni corrections revealed significant differences in Hemoglobin (Hb), White Blood Cell (WBC), Red Blood Cell (RBC), platelet, and Packed Cell Volume (PCV) levels before and after delivery (p < 0.05) in both groups. Elevated AST levels, but not other hematological or biochemical parameters, were independently associated with adverse pregnancy outcomes, whereas creatinine differences lacked clinical impact.

( Int J Gynaecol Obstet . 2026 Mar;172(3):1791–1793. doi: 10.1002/ijgo.70484) Obesity affects nearly 1 in 3 pregnancies and significantly elevates the risk of hypertensive disorders, which are major contributors to maternal illness and death. Accurate blood pressure (BP) monitoring is essential for managing these risks. However, traditional arm cuff methods often perform poorly in individuals with larger arm circumferences, particularly when compared with intra-arterial monitoring (A-line), which is considered the clinical gold standard. Despite its accuracy, the invasive nature and potential complications of A-line monitoring make it impractical for routine obstetric use.

BACKGROUND:Accurate HIV point of care testing is the cornerstone of prevention and treatment efforts globally, although false (both negative and positive) results are expected to occur. SETTING:We assessed the spectrum of true and false positive HIV results in a large prospective study of HIV incidence in African women using 3 contraceptive methods tested longitudinally in Eswatini, Kenya, South Africa, and Zambia. METHODS:HIV serologic testing was conducted quarterly using 2 parallel rapid HIV tests. When one or both tests were positive, additional confirmatory testing was conducted, including HIV enzyme immunoassay (EIA) and RNA. RESULTS:A total of 7730 women contributed 48,234 visits: true positive results occurred at 412 visits (0.9%) and false positives at 96 visits (0.2%). Of 412 women with HIV seroconversion, 10 had discordant (ie, 1 negative and 1 positive) rapid tests and 13 had undetectable HIV RNA levels. Of 62 women with false positive rapid HIV results, most had discordant rapid testing, but 6 (9.7%) had dually positive rapid results, and 4 (6.5%) had false positive or indeterminate EIA results. The positive predictive value of dual positive rapid results was 98.3%. CONCLUSIONS:Although most rapid test results were accurate, false positive results were expected and occurred in this population of initially HIV seronegative individuals tested repeatedly and prospectively. When HIV infection occurred, not all cases had textbook laboratory results. Our findings highlight the importance of confirmatory testing, particularly for individuals undergoing repeat testing and in settings where the point prevalence is expected to be low. TRIAL REGISTRATION:ClinicalTrials.gov number NCT02550067.

In low resource settings, twins often go undiagnosed until delivery. We sought to create a low-cost ultrasound tool for diagnosis and assessment of twins in settings where trained sonographers are scarce. We collected blind ultrasound sweeps (∼10 second cines in cranio-caudal and lateral directions) from pregnant people in North Carolina. The cohort was randomly divided at the patient level into discreet training/tuning (80%) and testing (20%) datasets. We built deep learning AI models to diagnose twins and estimate their gestational age (GA). We also explored assessment of chorionicity. From Feb 2020 thru March 2023, 16,557 pregnancies contributed 30,106 studies containing blind sweeps. Of these, 490 pregnancies (1,215 studies) were twins. To evaluate twin diagnosis, we restricted the test set to studies ≥14 weeks GA (3,163 pregnancies; 5,424 studies). Among the 87% of studies in which the model could make a prediction, the area under the receiver operating curve (AUC-ROC) was 99.4% (sens: 98.1%; spec: 98.2%). To evaluate twin GA estimation, we restricted the test set to twin pregnancies whose GA had previously been established by early CRL or IVF (92 pregnancies; 185 scans). The model made a prediction in all studies with a mean absolute error of 4.6 ±0.3 days vs 4.5 ±0.3 days for biometry (difference, 0.1 days; 95% CI: -0.6, 0.8). To evaluate chorionicity assessment, we limited the test set to twins with scans performed < 24 weeks (67 pregnancies, 93 scans). Among the 73% of studies in which the model could make a prediction, AUC-ROC was 87.1% (sens: 82.6%; spec: 82.2%). AI-assisted ultrasound, which can be deployed on low-cost point-of-care devices, can diagnose twins and assess their gestational age with high performance. Preliminary results for chorionicity assessment are encouraging but more training data from earlier GA are needed. These results presage a future where all patients carrying twins – not just those in rich countries – can access the diagnostic benefits of sonography.

OBJECTIVE:Low-cost devices have made obstetric sonography possible in settings where it was previously unfeasible, but ensuring quality and consistency at scale remains a challenge. In the present study, we sought to create a tool to reduce substandard fetal biometry measurement while minimizing care disruption. METHODS:We developed a deep learning artificial intelligence (AI) model to estimate gestational age (GA) in the second and third trimester from fly-to cineloops-brief videos acquired during routine ultrasound biometry-and evaluated its performance in comparison to expert sonographer measurement. We then introduced random error into fetal biometry measurements and analyzed the ability of the AI model to flag grossly inaccurate measurements such as those that might be obtained by a novice. RESULTS:The mean absolute error (MAE) of our model (±standard error) was 3.87 ± 0.07 days, compared to 4.80 ± 0.10 days for expert biometry (difference -0.92 days; 95% CI: -1.10 to -0.76). Based on simulated novice biometry with average absolute error of 7.5%, our model reliably detected cases where novice biometry differed from expert biometry by 10 days or more, with an area under the receiver operating characteristics curve of 0.93 (95% CI: 0.92, 0.95), sensitivity of 81.0% (95% CI: 77.9, 83.8), and specificity of 89.9% (95% CI: 88.1, 91.5). These results held across a range of sensitivity analyses, including where the model was provided suboptimal truncated fly-to cineloops. CONCLUSIONS:Our AI model estimated GA more accurately than expert biometry. Because fly-to cineloop videos can be obtained without any change to sonographer workflow, the model represents a no-cost guardrail that could be incorporated into both low-cost and commercial ultrasound devices to prevent reporting of most gross GA estimation errors.

ABSTRACT Background Copper (Cu), an essential trace mineral regulating multiple actions of inflammation and oxidative stress, has been implicated in risk for preterm birth (PTB). We aimed to determine the association of maternal plasma/serum Cu concentrations during pregnancy with PTB risk and gestational duration in a large multi-cohort study including diverse populations. Methods Gestational duration data and maternal plasma or serum samples of 10,449 singleton live births were obtained from 18 geographically diverse study cohorts. Maternal plasma or serum Cu concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) analysis. The associations of maternal Cu with PTB and gestational duration were analyzed using logistic and linear regressions for each cohort. The estimates were then combined using meta-analysis. Associations between maternal Cu and acute phase reactants (APRs), malaria, and HIV infection were analyzed in 1239 samples from the Malawi cohort. Findings The maternal prenatal Cu concentration in our study samples followed a normal distribution with a mean of 1.92 μg/ml and a standard deviation of 0.43 μg/ml, and Cu concentrations increased with gestational age up to 20 weeks. The random effect meta-analysis across the 18 cohorts revealed that 1 μg/ml increase in maternal Cu concentration before the third trimester was associated with a higher risk of PTB with an OR of 1.30 (95% CI: 1.08 to 1.57) and shorter gestational duration of 1.64 days (95% CI: 0.56 to 2.73). The estimated effects were generally consistent across all sites. In the Malawi cohort, higher maternal Cu concentration, concentrations of multiple APRs and infections (malaria and HIV) were correlated and associated with greater risk of PTB and shorter gestational duration. Interpretation Our study supports a robust negative association between maternal mid-gestation Cu concentration and gestational duration and a positive association with risk for preterm birth. Cu concentration was strongly correlated with APRs and infection status suggesting its potential role in inflammation, a pathway implicated in the mechanisms of PTB. Therefore, maternal Cu could be used as a potential marker of the integrated inflammatory pathways during pregnancy and risk for preterm birth.

Background. We evaluated associations between antepartum weight change and adverse pregnancy outcomes and between antiretroviral therapy (ART) regimens and week 50 postpartum body mass index in IMPAACT 2010. Methods. Women with human immunodeficiency virus (HIV)-1 in 9 countries were randomized 1:1:1 at 14-28 weeks' gestational age (GA) to start dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) versus DTG + FTC/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF. Insufficient antepartum weight gain was defined using Institute of Medicine guidelines. Cox-proportional hazards regression models were used to evaluate the association between antepartum weight change and adverse pregnancy outcomes: stillbirth (>= 20 weeks' GA), preterm delivery (<37 weeks' GA), small size for GA (<10th percentile), and a composite of these endpoints. Results. A total of 643 participants were randomized: 217 to the DTG + FTC/TAF, 215 to the DTG + FTC/TDF, and 211 to the EFV/FTC/TDF arm. Baseline medians were as follows: GA, 21.9 weeks; HIV RNA, 903 copies/mL; and CD4 cell count, 466/mu L. Insufficient weight gain was least frequent with DTG + FTC/TAF (15.0%) versus DTG + FTC/TDF (23.6%) and EFV/FTC/TDF (30.4%). Women in the DTG + FTC/TAF arm had the lowest rate of composite adverse pregnancy outcome. Low antepartum weight gain was associated with higher hazard of composite adverse pregnancy outcome (hazard ratio, 1.44 [95% confidence interval, 1.04-2.00]) and small size for GA (1.48 [.99-2.22]). More women in the DTG + FTC/TAF arm had a body mass index >= 25 (calculated as weight in kilograms divided by height in meters squared) at 50 weeks postpartum (54.7%) versus the DTG + FTC/TDF (45.2%) and EFV/FTC/TDF (34.2%) arms. Conclusions. Antepartum weight gain on DTG regimens was protective against adverse pregnancy outcomes typically associated with insufficient weight gain, supportive of guidelines recommending DTG-based ART for women starting ART during pregnancy. Interventions to mitigate postpartum weight gain are needed.

M-estimation is a statistical procedure that is particularly advantageous for some comon epidemiological analyses, including approaches to estimate an adjusted marginal risk contrast (i.e. inverse probability weighting and g-computation) and data fusion. In such settings, maximum likelihood variance estimates are not consistent. Thus, epidemiologists often resort to bootstrap to estimate the variance. In contrast, M-estimation allows for consistent variance estimates in these settings without requiring the computational complexity of the bootstrap. In this paper, we introduce M-estimation and provide four illustrative examples of implementation along with software code in multiple languages. M-estimation is a flexible and computationally efficient estimation procedure that is a powerful addition to the epidemiologist's toolbox.

Postpartum depression (PPD) affects nearly 20% of postpartum women in Sub-Saharan Africa (SSA), where HIV prevalence is high. Depression is associated with worse HIV outcomes in non-pregnant adults and mental health disorders may worsen HIV outcomes for postpartum women and their infants. PPD is effectively treated with psychosocial or pharmacologic interventions; however, few studies have evaluated the acceptability of treatment modalities in SSA. We analyzed interviews with 23 postpartum women with HIV to assess the acceptability of two depression treatments provided in the context of a randomized trial. Most participants expressed acceptability of treatment randomization and study visit procedures. Participants shared perceptions of high treatment efficacy of their assigned intervention. They reported ongoing HIV and mental health stigma in their communities and emphasized the importance of social support from clinic staff. Our findings suggest a full-scale trial of PPD treatment will be acceptable among women with HIV in Zambia.